Safety and Immunogenicity of 2 Formulations of Tuberculosis Vaccine GSK692342 Given at 0,1 Months to Healthy Adults
2019年6月6日 更新者：GlaxoSmithKline
Safety, Reactogenicity & Immunogenicity of 2 Formulations of Tuberculosis Vaccine GSK692342 Administered Intramuscularly According to a Schedule of 0, 1 Month, to Healthy Adults Aged 18 to 50 Years
This study will assess the safety and immunogenicity of 2 different formulations of tuberculosis vaccine GSK692342 in healthy adults.
調査の概要
状態
完了
条件
詳細な説明
The study is designed to have a vaccination phase (includes screening, 2 doses of vaccine 1 month apart and follow-up until 1 month post dose 2), which will be performed in an observer blinded manner. This will be followed by 3 years of follow-up which will continue in an open manner.
No new subjects will be recruited at the follow-up phase. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
研究の種類
介入
入学 (実際)
110
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Gent、ベルギー、9000
- GSK Investigational Site
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年～50年 (大人)
健康ボランティアの受け入れ
はい
受講資格のある性別
全て
説明
Inclusion Criteria:
- Subjects who the investigator believes that they can and will comply with the requirements of the protocol
- A male or female between, and including, 18 and 50 years of age at the time of the first vaccination.
- Written informed consent obtained from the subject prior to any study procedure.
- Free of obvious health problems as established by medical history and clinical examination before entering into the study.
- Subjects must have PPD negative skin reactivity (0 mm induration 48 to 72 hours after PPD skin test administration).
- Clinically normal laboratory values for creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), complete blood count (CBC) and differential, haemoglobin, platelet count and urinalysis.
- Seronegative for human immunodeficiency virus-1 and 2 (HIV 1/2) antibodies, hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) antibodies
- If the subject is female, she must be of non-childbearing potential, or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions for 30 days prior to vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after completion of the vaccination series.
- No evidence of pulmonary pathology (i.e. acute or chronic pulmonary disease; past TB infection/disease) as confirmed by chest X-ray.
Exclusion Criteria:
- History of previous exposure to experimental products containing components of the experimental vaccine.
- Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.
- Chronic administration of immunosuppressants or other immune-modifying drugs within 6 months prior to the first vaccine dose.
- Any chronic drug therapy to be continued during the study period. Vitamins and/or dietary supplements, herbal medications, birth control pills, anti-histamines for seasonal allergies, SSRIs (e.g. Prozac, Zoloft, Paxil), NSAIDs (nonsteroidal anti-inflammatory drugs e.g. aspirin, ibuprofen), and acetaminophen are allowed.
- History of documented exposure to Mycobacterium tuberculosis.
- History of prior vaccination with experimental Mycobacterium tuberculosis vaccines.
- Administration of any immunoglobulins, any immunotherapy and/or any blood products within the 3 months preceding the first dose of study vaccination, or planned administrations during the study period.
- Participation in another experimental protocol during the study period.
- Any confirmed or suspected immunosuppressive or immunodeficient condition; or family history of congenital or hereditary immunodeficiency.
- History of hypersensitivity to vaccines or vaccine components
- History of any acute or chronic illness or medication that, in the opinion of the investigator, may interfere with the evaluation of the safety or immunogenicity of the vaccine.
- Volunteers with a personal history of autoimmune disease or who describe a first-degree relative with clearly documented autoimmune disease.
- History of any neurological disorders or seizures.
- History of chronic alcohol consumption and/or drug abuse.
- History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
- Major congenital defects.
- Pregnant female, lactating female or female planning to become pregnant or planning to discontinue contraceptive precautions.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：防止
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：M72/AS01B Group
Healthy male or female subjects, between and including 18 to 50 years of age, who received 2 doses of M72/AS01B vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 0 and Month 1.
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筋肉注射、0時2回、1ヶ月
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実験的：M72/AS02A Group
Healthy male or female subjects, between and including 18 to 50 years of age, who received 2 doses of M72/AS02A vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 0 and Month 1.
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筋肉注射、0時2回、1ヶ月
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アクティブコンパレータ：Mtb72F/AS02A Group
Healthy male or female subjects, between and including 18 to 50 years of age, who received 2 doses of the comparator Mtb72F/AS02A vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 0 and Month 1.
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Intramuscular injection, 2 doses at 0, 1 month
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アクティブコンパレータ：Non-adjuvanted Group
Healthy male or female subjects, between and including 18 to 50 years of age, who received 2 doses of the comparator GSK Biologicals' candidate recombinant M. tuberculosis vaccine, non-adjuvanted, administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 0 and Month 1.
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生物学的：Comparator vaccine with recombinant Mycobacterium tuberculosis antigen and physiological saline
Intramuscular injection, 2 doses at 0, 1 month
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プラセボコンパレーター：Control Group
Healthy male or female subjects, between and including 18 to 50 years of age, who received 2 doses of the adjuvant system alone, administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 0 and Month 1.
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筋肉注射、0時2回、1ヶ月
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Number of Subjects With Any and Grade 3 Solicited Local Symptoms
時間枠：During the 7-day (Days 0-6) follow-up period after each vaccine dose and across doses
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Assessed solicited local symptoms were pain, redness and swelling.
Any = occurrence of the symptom regardless of intensity grade.
Grade 3 pain = pain that prevented normal activity.
Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site.
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During the 7-day (Days 0-6) follow-up period after each vaccine dose and across doses
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Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
時間枠：During the 7-day (Days 0-6) follow-up period after each vaccine dose and across doses
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Assessed solicited general symptoms were fatigue, fever [defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)], gastrointestinal symptoms and headache.
Any = occurrence of the symptom regardless of intensity grade.
Grade 3 symptom = symptom that prevented normal activity.
Grade 3 fever = fever > 39.5 °C.
Related = symptom assessed by the investigator as causally related to the study vaccination.
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During the 7-day (Days 0-6) follow-up period after each vaccine dose and across doses
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Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
時間枠：During the 30-day (Days 0-29) follow-up period after each vaccine dose
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An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.
Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
Grade 3 AE = an AE which prevented normal, everyday activities.
Related = AE assessed by the investigator as related to the vaccination.
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During the 30-day (Days 0-29) follow-up period after each vaccine dose
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Number of Subjects With Serious Adverse Events (SAEs)
時間枠：During the Active Vaccination Phase (from Day 0 up to Month 2)
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SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
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During the Active Vaccination Phase (from Day 0 up to Month 2)
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Number of Subjects With SAEs
時間枠：From Month 2 up to Month 12
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SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
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From Month 2 up to Month 12
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Number of Subjects With SAEs
時間枠：From Month 12 up to Month 24
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SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Note: Follow-up during Year 2 continued only for the M72/AS01B Group and M72/AS02A Group.
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From Month 12 up to Month 24
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Number of Subjects With SAEs
時間枠：From Month 24 up to Month 36
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SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Note: Follow-up during Year 3 continued only for the M72/AS01B Group and M72/AS02A Group.
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From Month 24 up to Month 36
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Number of Subjects With Normal or Abnormal Haematological and Biochemical Levels
時間枠：At Day 0
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Among haematological and biochemical parameters assessed were Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Basophils, Creatinine, Eosinophils, Haemoglobin, Haematocrite, Lymphocytes, Monocytes, Neutrophils, Platelets, Red blood cells (RBC), White blood cells (WBC).
Inside = within laboratory reference range; Above = above laboratory reference range; Below = below laboratory reference range.
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At Day 0
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Number of Subjects With Normal and Abnormal Haematological and Biochemical Levels
時間枠：At Day 7
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Among haematological and biochemical parameters assessed were Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Basophils, Creatinine, Eosinophils, Haemoglobin, Haematocrite, Lymphocytes, Monocytes, Neutrophils, Platelets, Red blood cells (RBC), White blood cells (WBC).
Inside = within laboratory reference range; Above = above laboratory reference range; Below = below laboratory reference range.
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At Day 7
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Number of Subjects With Normal or Abnormal Haematological and Biochemical Levels
時間枠：At Day 30
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Among haematological and biochemical parameters assessed were Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Basophils, Creatinine, Eosinophils, Haemoglobin, Haematocrite, Lymphocytes, Monocytes, Neutrophils, Platelets, Red blood cells (RBC), White blood cells (WBC).
Inside = within laboratory reference range; Above = above laboratory reference range; Below = below laboratory reference range.
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At Day 30
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Number of Subjects With Normal or Abnormal Haematological and Biochemical Levels
時間枠：At Day 37
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Among haematological and biochemical parameters assessed were Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Basophils, Creatinine, Eosinophils, Haemoglobin, Haematocrite, Lymphocytes, Monocytes, Neutrophils, Platelets, Red blood cells (RBC), White blood cells (WBC).
Inside = within laboratory reference range; Above = above laboratory reference range; Below = below laboratory reference range.
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At Day 37
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Number of Subjects With Normal or Abnormal Haematological and Biochemical Levels
時間枠：At Day 60
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Among haematological and biochemical parameters assessed were Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Basophils, Creatinine, Eosinophils, Haemoglobin, Haematocrite, Lymphocytes, Monocytes, Neutrophils, Platelets, Red blood cells (RBC), White blood cells (WBC).
Inside = within laboratory reference range; Above = above laboratory reference range; Below = below laboratory reference range.
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At Day 60
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Levels of C-reactive Protein
時間枠：At Day 0
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The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
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At Day 0
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Levels of C-reactive Protein
時間枠：At Day 1
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The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
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At Day 1
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Levels of C-reactive Protein
時間枠：At Day 7
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The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
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At Day 7
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Levels of C-reactive Protein
時間枠：At Day 30
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The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
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At Day 30
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Levels of C-reactive Protein
時間枠：At Day 31
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The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
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At Day 31
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Levels of C-reactive Protein
時間枠：At Day 37
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The levels of C-reactive protein are expressed in milligram per deciliter (mg/dL).
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At Day 37
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Levels of Immunoglobulin E
時間枠：At Day 0
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The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
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At Day 0
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Levels of Immunoglobulin E
時間枠：At Day 1
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The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
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At Day 1
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Levels of Immunoglobulin E
時間枠：At Day 7
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The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
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At Day 7
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Levels of Immunoglobulin E
時間枠：At Day 30
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The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
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At Day 30
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Levels of Immunoglobulin E
時間枠：At Day 31
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The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
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At Day 31
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Levels of Immunoglobulin E
時間枠：At Day 37
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The levels of Immunoglobulin E are expressed in 1000 units per liter (1000 U/L).
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At Day 37
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Antibody Concentrations Against Mycobacterium Tuberculosis (M. Tuberculosis) Fusion Proteins M72 and Mtb72F
時間枠：At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)
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Antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in Enzyme-Linked Immunosorbent Assay (ELISA) units per milliliter (EU/mL).
The reference seropositivity cut-off values for anti-M72 and anti-Mtb72F antibodies were ≥ 2.8 EU/mL and ≥ 1.0 EU/mL, respectively.
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At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)
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Antibody Concentrations Against M. Tuberculosis Fusion Protein M72
時間枠：At Year 2 (Month 24) and Year 3 (Month 36)
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Antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EU/mL).
The reference seropositivity cut-off value for anti-M72 antibodies was ≥ 2.8 EU/mL.
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At Year 2 (Month 24) and Year 3 (Month 36)
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Frequency of Mycobacterium Tuberculosis Fusion Protein (M72) Specific Cluster of Differentiation 4/8 (CD4/CD8+) T-cells Expressing at Least Two Different Cytokines
時間枠：At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)
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Among cytokines expressed were interleukin-2 [IL-2] and/or interferon-gamma [IFN-γ] and/or tumour necrosis factor-alpha [TNF-α] and/or cluster of differentiation 40-ligand [CD40-L].
The analysis of cytokines expression was performed by flow cytometry using intracellular cytokine staining (ICS) on frozen peripheral blood mononuclear cell (PBMCs).
Note: No vaccine induced responses were observed for CD8+ T-cells, so no results are presented throughout the record.
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At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)
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Frequency of Mycobacterium Tuberculosis Fusion Protein (M72) Specific Cluster of Differentiation 4 (CD4+) T-cells Expressing at Least Two Different Cytokines
時間枠：At Year 2 (Month 24) and Year 3 (Month 36)
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Among cytokines expressed were interleukin-2 [IL-2] and/or interferon-gamma [IFN-γ] and/or tumour necrosis factor-alpha [TNF-α] and/or cluster of differentiation 40-ligand [CD40-L].
The analysis of cytokines expression was performed by flow cytometry using intracellular cytokine staining (ICS) on frozen peripheral blood mononuclear cell (PBMCs).
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At Year 2 (Month 24) and Year 3 (Month 36)
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Frequency of M72 Specific CD4+ T-cells Expressing at Least One Cytokine and Another Signal Molecule
時間枠：At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)
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Expressed cytokine combinations for CD4+ T-cells were CD40-L and interleukin-2 [IL-2] or interferon-gamma [IFN-γ] or tumour necrosis factor-alpha [TNF-α]; IL-2 and CD40-L, or IFN-γ, or TNF-α; IFN-γ and CD40-L, or IL-2, or TNF-α; TNF-α and CD40-L, or IL-2, or IFN-γ.
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At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)
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Frequency of M72 Specific CD4+ T-cells Expressing at Least One Cytokine and Another Signal Molecule
時間枠：At Year 2 (Month 24) and Year 3 (Month 36)
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Expressed cytokine combinations for CD4+ T cells were CD40-L and interleukin-2 [IL-2] or interferon-gamma [IFN-γ] or tumour necrosis factor-alpha [TNF-α]; IL-2 and CD40-L, or IFN-γ, or TNF-α; IFN-γ and CD40-L, or IL-2, or TNF-α; TNF-α and CD40-L, or IL-2, or IFN-γ.
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At Year 2 (Month 24) and Year 3 (Month 36)
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Number of Subjects With Response to M72-specific CD4+ T-cells Secreting at Least Two Different Cytokines/Activation Markers
時間枠：At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)
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The cut-off value used for analysis of the frequency of cells expressing cytokines/immune markers was the 313 CD4+ T-cells per million CD4+ T-cells, i.e. the 95th percentile of the pre-vaccination level of cells expressing cytokines/immune markers.
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At Day 0, prior to Dose 2 (Month 1), 1 month post-Dose 2 (Month 2) and Year 1 (Month 12)
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Number of Subjects With Response to M72-specific CD4+ T-cells Secreting at Least Two Different Cytokines/Activation Markers
時間枠：At Year 2 (Month 24) and Year 3 (Month 36)
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The cut-off value used for analysis of the frequency of cells expressing cytokines/immune markers was the 313 CD4+ T-cells per million CD4+ T-cells, i.e. the 95th percentile of the pre-vaccination level of cells expressing cytokines/immune markers.
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At Year 2 (Month 24) and Year 3 (Month 36)
|
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Concentrations of IFN-γ Produced in Serum Samples
時間枠：Prior to (Day 0 and Day 30) and one day (Day 1 and Day 31) after each vaccination
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Concentrations are presented as geometric mean concentrations (GMCs), expressed in picogram per milliliter (pg/mL).
The reference seropositivity cut-off value was equal to or above (≥) 1 pg/mL.
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Prior to (Day 0 and Day 30) and one day (Day 1 and Day 31) after each vaccination
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- Moris P, Bellanger A, Ofori-Anyinam O, Jongert E, Yarzabal Rodriguez JP, Janssens M. Whole blood can be used as an alternative to isolated peripheral blood mononuclear cells to measure in vitro specific T-cell responses in human samples. J Immunol Methods. 2021 May;492:112940. doi: 10.1016/j.jim.2020.112940. Epub 2021 Jan 23.
- Leroux-Roels I, Forgus S, De Boever F, Clement F, Demoitie MA, Mettens P, Moris P, Ledent E, Leroux-Roels G, Ofori-Anyinam O; M72 Study Group. Improved CD4(+) T cell responses to Mycobacterium tuberculosis in PPD-negative adults by M72/AS01 as compared to the M72/AS02 and Mtb72F/AS02 tuberculosis candidate vaccine formulations: a randomized trial. Vaccine. 2013 Apr 19;31(17):2196-206. doi: 10.1016/j.vaccine.2012.05.035. Epub 2012 May 27.
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2006年11月15日
一次修了 (実際)
2009年12月1日
研究の完了 (実際)
2009年12月1日
試験登録日
最初に提出
2006年11月9日
QC基準を満たした最初の提出物
2006年11月9日
最初の投稿 (見積もり)
2006年11月10日
学習記録の更新
投稿された最後の更新 (実際)
2019年6月19日
QC基準を満たした最後の更新が送信されました
2019年6月6日
最終確認日
2019年6月1日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- 106227
- 106228 (その他の識別子：GSK)
- 108736 (その他の識別子：GSK)
- 108738 (その他の識別子：GSK)
- 2005-004497-24 (EudraCT番号)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
はい
IPD プランの説明
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。